Brain

A study published March 16 in JAMA (the Journal of the American Medical Association) confirms that neither vitamin D nor the omega-3 fatty acids found in fish oil prevent the development of atrial fibrillation (AF), a potentially serious heart rhythm disturbance. The newly published research follows a presentation made by Christine Albert, MD, MPH, at the American Heart Association Scientific Sessions last year.

In their JAMA analysis, Albert and her research team also examined whether vitamin D or omega-3 fatty acids might have an impact on paroxysmal versus persistent atrial fibrillation and whether there might be certain subgroups of patients who would be more likely to benefit or be harmed by the supplements. Overall, the results were mostly consistent across types of AF and groups of patients.

"Our recommendation remains the same," said Albert, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology. "We do not support taking fish oil or vitamin D supplements to prevent atrial fibrillation."

Albert added, "However, unlike other recent trials that found increased risks of atrial fibrillation with higher-dose omega-3 fatty acid supplements, our study did not find a significantly increased risk of atrial fibrillation with one gram of fish oil per day, which is good news for individuals taking low-dose fish oil for other health conditions."

Similarly, vitamin D supplements at 2,000 international units per day also did not increase AF risk.

Atrial fibrillation, commonly called Afib, is the most common type of abnormal heart rhythm, causing the heart to contract irregularly and, sometimes, too quickly. It is estimated to affect 33 million people worldwide.

The condition can lead to clotting inside the atrium chamber of the heart and clots can then travel from the heart to the brain, causing a stroke. Atrial fibrillation can also lead to weakening of the bottom chamber of the heart, resulting in fluid buildup or heart failure. Importantly, it often results in significant symptoms that can adversely affect one's quality of life.

The activity of enzymes in industrial processes, laboratories, and living beings can be remotely controlled using light. This requires their immobilization on the surface of nanoparticles and irradiation with a laser. Near-infrared light can penetrate living tissue without damaging it. The nanoparticles absorb the energy of the radiation and release it back in the form of heat or electronic effects, triggering or intensifying the enzymes' catalytic activity. This configures a new field of study known as plasmonic biocatalysis.

Research conducted at the University of São Paulo's Chemistry Institute (IQ-USP) in Brazil investigated the activity of enzymes immobilized on gold nanoparticles controlled by infrared laser irradiation. An article reporting the results is published in ACS Catalysis, a journal of the American Chemical Society.

The study was supported by São Paulo Research Foundation - FAPESP via a postdoctoral fellowship and a scholarship for a research internship abroad awarded to the lead author, Heloise Ribeiro de Barros; a multiuser equipment grant; and the Thematic Project "Optimization of the physicochemical properties of nanostructured materials for applications in molecular recognition, catalysis and energy conversion/storage", led by Roberto Manuel Torresi.

"We used a lipase [CaLB] as the model enzyme, immobilized on gold nanoparticles with two shapes - spheres and stars," Ribeiro de Barros told. "The infrared laser accelerated the enzyme's activity non-invasively merely by irradiating it with external light."

The study showed that not only the composition of the material but also its geometry influenced the effect of the nanoparticles on the enzyme. "The enzymatic activity was significantly enhanced when the lipase was immobilized on gold nanostars, displaying an increase of up to 58%," Ribeiro de Barros said. "In comparison, the gold nanospheres promoted a much smaller increase of 13%. The larger increase corresponded to the effect of resonance between the surfaces of the nanostars and radiation from the laser."

The magnitude considered here is localized surface plasmon resonance (LSPR). While the LSPR of the nanospheres absorbs at 525 nanometers, that of the nanostars reaches 700 nm, much closer to the infrared laser wavelength, which is 808 nm.

"The incident light sets off energy-driven processes in the gold nanoparticles, such as a rise in temperature or electronic effects, and this affects the properties of the enzymes that are immobilized on their surfaces," Ribeiro de Barros said. "It was possible to conclude that localized photothermal heating on the surfaces of the gold nanostars promoted by LSPR excitation led to enhanced lipase biocatalysis. This conclusion can be extended to other combinations of enzymes and plasmonic nanoparticles."

The wide array of potential applications includes biocatalysis to accelerate industrial-scale chemical reactions and in vivo control of disease-causing enzymes. In the more distant future, this kind of process could conceivably be used to treat diseases such as Parkinson's and Alzheimer's. More research will be required before it can become a genuine alternative, of course.

"From the medical standpoint, the main purpose of the study was to point to solutions in the near future for the treatment of diseases without the need for invasive surgery and with a specific spatial and temporal approach to avoid the side-effects of current methods," Ribeiro de Barros said.

It would surprise no one that pursuing a graduate degree can be a stressful endeavor, and for students who are transgender and nonbinary (TNB), the atmosphere can become toxic, according to University of Houston researcher Nathan Grant Smith. In a new paper published in Higher Education, Smith provides an analysis of current literature pertaining to TNB graduate student experiences and suggests interventions in graduate education to create more supportive environments for TNB students.

"Nearly 50% of graduate students report experiencing emotional or psychological distress during their enrollment in graduate school. Levels of distress are particularly high for transgender and nonbinary graduate students who experience daily discrimination and marginalization," reports Smith, associate professor in the counseling psychology doctoral program at the UH College of Education and chair of the Department of Psychological, Health, and Learning Sciences.

In compiling and analyzing the literature, Smith was joined by Douglas Knutson of Oklahoma State University. Their team included Em Matsuno, Palo Alto University; Chloe Goldbach, Southern Illinois University Carbondale; and Halleh Hashtpari, The University of Utah.

The existing literature suggests that discrimination against TNB college students is increasing and that discrimination on college campuses (e.g., reduced access to housing, restricted access to bathrooms and locker rooms) is associated with negative psychological outcomes such as suicidal ideation. Smith and team offer a social-ecological model of transgender stigma and stigma interventions.

"We are providing a framework for understanding that people interact with the outside world at different levels," said Smith. "Those levels are one-on-one, interpersonal with groups and structural with interactions between policies and norms of an institution."

Since all levels are connected, Smith suggests everyone start by doing their own exploration of gender and challenge their internal biases that will surely impact others. For example, consider how your gender identity helped or hindered your current career path and other life experiences. Reflect on which gender pronouns you use (e.g., he/him/ his, she/her/hers, they/them/theirs) and how you would feel if others repeatedly used incorrect pronouns when talking to or about you.

"Students who are trained in TNB-affirmative environments will enter the workforce, equipped to cultivate more empowering and diverse spaces for their colleagues, their families, and for the communities in which they live," said Smith. "We encourage everyone to think of TNB inclusion as an opportunity and as an affective experience based in empathy, love, and an impulse toward community building."

Some of the team's recommendations include:

Creating affirming spaces for TNB graduate students

Reviewing - and making inclusive - university paperwork, such as applications, intake forms for student services (like counseling and health), program handbooks, course syllabi, website pages, faculty pages and student evaluations
Inclusion of gender-affirming care in student insurance plans
Training of counseling center and health center staff

"These and other steps are crucial for building a foundation of empathy and humility in order to provide safe, inclusive and affirming spaces for TNB graduate students," Smith reported.

Bring on Twilight. Lee Child's Jack Reacher? Yes, please. More of James Patterson's Alex Cross while we're at it. And let's finish off with revisiting the million-plus words of the Harry Potter saga.

No one will confuse the above book series with high literature. But a new study published in the journal Reading and Writing shows that the more people read any kind of fiction -- even mass market stuff sniffily derided as pulp -- the better their language skills are likely to be.

The piece was written by Sandra Martin-Chang, professor of education in the Faculty of Arts and Science, and PhD student Stephanie Kozak. They found that people who enjoyed reading fiction for leisure and who identified as a reader scored higher on language tests, whereas those who read to access specific information scored more poorly on the same tests. Kyle Levesque of Dalhousie University, Navona Calarco of Toronto's Centre for Addiction and Mental Health, and Raymond Mar of York University also co-authored the paper.

As leisure reading declines as a pastime for younger adults especially, Martin-Chang says emphasizing the fun aspect of it can draw them back to novels while at the same time boost their verbal abilities.

"It's always very positive and heartening to give people permission to delve into the series that they like," Martin-Chang notes. "I liken it to research that says chocolate is good for you: the guilty pleasure of reading fiction is associated with positive cognitive benefits and verbal outcomes."

Habit-forming pastime

Martin-Chang and Kozak used a scale developed by Mar called the Predictors of Leisure Reading (PoLR) to investigate reading behaviour (motivations, obstacles, attitudes and interests). They then examined how well the PoLR predicted the language skills of 200 undergraduate students, with all data gathered at York University.

The researchers note that the age range of the subjects in the study is of key interest. In early adulthood, reading becomes self-directed rather than imposed by others, which makes this a pivotal time for developing one's own reading habits. This population is also rather understudied, with most existing research focusing far more on children.

The researchers administered a series of measures over two separate half-hour sessions. First, the volunteers completed the 48-question PoLR scale measuring various reading factors. They were then given language tests similar to those found in the SAT and a measure of reading habits called the Author Recognition Test. This test asks respondents to select the names of real fiction and non-fiction authors they are familiar with from a long list of real and fake names. Scores on this test correlate with both actual reading behaviour and with verbal abilities: those who scored higher read more and have better verbal abilities than those who scored lower.

After analyzing the data, the researchers concluded that reading enjoyment, positive attitudes and deeply established interests predict better verbal abilities and that they were more strongly associated with exposure to fiction than non-fiction.

The written word: a love story

The many benefits of reading have long been established. Besides having better verbal abilities, lifelong readers are known to be more understanding of others, more empathetic, less prejudiced, to attain higher socioeconomic status and even to live longer, healthier lives than non-readers.

Teachers and parents can nurture a love of reading by letting young people read what they want, without guilt or shame.

"This ingrained interest, wanting to read something over and over again, feeling compelled to read an entire series, feeling connected to characters and authors, these are all good things," Martin-Chang concludes.

AUSTIN, Texas -- Using NASA satellite images and machine learning, researchers with The University of Texas at Austin have mapped changes in the landscape of northwestern Belize over a span of four decades, finding significant losses of forest and wetlands, but also successful regrowth of forest in established conservation zones that protect surviving structures of the ancient Maya.

The research serves as a case study for other rapidly developing and tropical regions of the globe, especially in places struggling to balance forest and wetland conservation with agricultural needs and food security.

"Broad-scale global studies show that tropical deforestation and wetland destruction is occurring rapidly, which contributes to climate change in multiple ways such as through greenhouses gas increases," said Timothy Beach, the study's co-author and professor in the Department of Geography and the Environment at UT Austin. "These also lead to more runoff and water pollution in much of the Global South. Belize has served as our long-term environmental research laboratory for this global dilemma."

In a study published in Remote Sensing, the team led by UT Austin graduate student Colin Doyle used satellite images from NASA's Landsat archive to quantify land-use and land-cover (LULC) changes that occurred in Belize's Orange Walk District in 1984-1987, 1999-2001 and 2014-2016. The periods were chosen to correspond with rapid changes in the agricultural system and conservation initiatives.

The Landsat program, which has been recording images of Earth since 1972, is currently on its eighth satellite. To study such broad periods, the authors used images from Landsat 8 and earlier satellites and employed a multitemporal approach, creating composite images from wet and dry seasons over several years for each period. They then trained an algorithm to identify eight distinct land types, including several varieties of forest and wetlands. From this, they generated maps illustrating the LULC for each of the three periods.

During the first period (1984-1987), deforestation was limited to small patches resulting from milpa farming -- a system of rotating crops and allowing previous plots to lie fallow in between use to maximize yields.

Several protected areas were established in the late 1980s and early 1990s. By the second period examined (1999-2001), forests in these protected areas had regrown but losses to wetlands continued, as did the conversion of nonprotected land to agriculture.

The third period mapped (2014-2016) followed a shift to industrial agriculture in the 2000s and showed "alarming" losses to both forest (7.5% loss) and wetlands (28.2% loss) outside of protected areas, said co-author Sheryl Luzzadder-Beach, the founding director of the university's Water Quality & Environmental Hydrology Lab.

Population growth contributed to the increase in land used for agriculture. However, it was a greater factor between the first and second periods, when the population nearly doubled, than between the second and third periods, when population grew more slowly, indicating that changes in farming practices had a greater impact on land use.

The maps also revealed the importance of conservation efforts in maintaining forests. Of the remaining forest in the study area, 76% is estimated to be on protected lands. These habitats are crucial in housing native flora and fauna and also contain structures from the Maya civilization important to the region's cultural heritage.

"These ecosystems provide many services such as aiding in the water cycle and preventing flooding," Doyle said. "The conversion of forest to pastureland and industrial agriculture is also a major contributor to increasing greenhouse gas emissions across the tropics."

Osaka, Japan - Synthesizing pharmaceuticals for cancer, viral diseases, and other medical conditions is slow work. A particularly challenging chemical transformation is to start with what's known as an unactivated alkene—a common molecular building block—and end up with a vicinal diamine; i.e., installation of two nitrogen units into carbon—carbon double bonds. The result is a chemical unit that's present in medications for influenza and colorectal cancer.

Commonly, researchers must use rare, toxic metals and harsh reaction conditions to complete this transformation. Using a more sustainable catalyst for the reaction could solve such problems. Previous research has attempted to do so, yet with only limited success.

In a study recently published in the Journal of the American Chemical Society, researchers from Osaka University synthesized vicinal diamines from unactivated alkenes, using iodine as the catalyst. The synthetic protocol, appropriate for both anti- and syn-addition, is realistic, useful, and environmentally friendly.

"We synthesized all diastereomers of vicinal diamines by anti-addition—adding two substituents to opposite sides of the double bond," says Satoshi Minakata, lead and senior author. "In the presence of a molecular iodine catalyst, unactivated alkenes reacted with commercially available nosylamide and sodium hypochlorite, to yield the intended products in a stereospecific manner."

The reactions were complete within 12 hours at only 40°C for many types of cyclic and terminal alkenes, such as styrene derivatives. Diaminating an internal alkene with precise control of the three-dimensional shape of the final reaction products—important in many drug molecules—required only minor adjustments to the reaction temperature.

"Syn-addition—adding one or more substituents to the same sides of the double bond—required a different yet still mild reaction protocol," says Hayato Miwa, second author. "The alkene substrate scope for syn-addition was broad: we even fused heteroaromatic compounds across the bond."

A common limitation of previous vicinal diamine syntheses is the last step: removal of protecting groups—rather inert chemical units that mask the chemistry of one or more chemical units in the molecule. Protecting groups prevent otherwise reactive units in the molecule from interfering with the reaction at hand. The Osaka University researchers found that removing the protecting groups from the amines at the end of their syntheses was straightforward.

"The main byproducts of our protocol are sodium chloride and water," says Minakata. "We are doing our best to minimize the environmental impact of an important chemical reaction."

By using molecular iodine as the catalyst, instead of a toxic or rare metal, Minakata and coworkers are advancing the sustainability of pharmaceutical syntheses for future generations. Their approach will also help minimize possible chemical supply chain disruptions over the course of the ongoing pandemic.

CORVALLIS, Ore. - Oregon State University researchers analyzed more than 17,000 public comments focused on orca conservation in the state of Washington and found that the most common emotional sentiments were trust, anticipation and fear.

The recently published findings have important implications because they provide conservation managers a way to convert a large volume of information to a manageable amount that can help them understand why people might support or reject management actions, the researchers said.

"Emotions are intertwined in our decision-making, often playing a substantive role in public evaluations of conservation policies," said Kelly Biedenweg, an author of the study and an assistant professor at Oregon State who studies psychology in the field of conservation.

"In this context, because we had such a high combination of trust and fear and sadness, that actually is the perfect combination for implementing more conservation-based strategies because in that emotional state people are more willing to take protective actions. Whereas if people were angry, that would be bad time to implement those protective conservation strategies."

Orcas have long captured human attention for their complex behaviors and social structure. They are also an icon of the Pacific Northwest, where they are depicted in Indigenous art, featured on license plates and a driver of tourism.

Since 1996, Southern Resident orcas, the population that resides in Pacific Northwest waters, have experienced steady decline and were listed as endangered in 2005, the researchers say in the study published in the journal Conservation Science and Practice. The most critical issues to their recovery are pollution, vessel disturbance and prey availability.

The decline of orcas spurred Washington governor Jay Inslee to create a task force in 2018 to develop recommendations for orca recovery. From July 2018 through May 2019, the governor's office received more than 17,000 public comments regarding orca conservation. The large volume of public comments was in part due to several high profile orca deaths in that region during that time, including a newborn calf that died and was carried by its mother for 17 days.

The Oregon State study, led by Hailey Kehoe-Thommen, an undergraduate Honors College student who has since graduated, used an emotion lexicon that categorizes 14,000 words into eight basic emotions: joy, trust, fear, surprise, sadness, anticipation, anger and disgust.

The researchers worked with a separate team at the Center for Applied Systems & Software at Oregon State to develop a computer program that merged that lexicon with the words from the 17,000 public comments the orca task force received.

The computer program found words associated with trust in 22% of the comments, the most common of any of the eight emotion categories. Findings in the remaining categories were as follows: anticipation (18%), fear (15%), joy (11%), sadness (11%), surprise (8%), anger (8%) and disgust (7%).

Trust was most associated with words such as save, food and governor; anticipation with time, immediately and plan; fear with watching, remove and endangered; sadness with remove, problem and death; surprise with wild, good and death; anger with remove, death and money; and disgust with pollution, creatures and death.

The fact that "trust" was the most common category leads the researchers to believe that respondents have strong faith that if particular actions are taken the orcas can be saved. Furthermore, the fact that one of the most frequently used words in the trust category was "governor" suggests that respondents have some level of recognition and acceptance of this person's power to resolve the situation.

This type of finding could lead conservation organizations to build on the public acceptance of the governor's power and develop strategic actions and messaging that establish the governor's office as leading efforts to implement orca conservation, the Oregon State researchers conclude.

While the orca task force in Washington has already issued a report and recommendations, this type of analysis could be valuable in other conservation situations where there is a large volume of public comments, Biedenweg said.

"Teasing apart specific emotions to all of these issues is going to help us have a much more nuanced vision of why people are reacting in certain ways and how we might incorporate those reactions into policy," she said.

A fear of poor SATs results is driving headteachers to separate pupils by ability despite the impact on children's self-esteem and confidence, according to a study by researchers from UCL published in the peer-reviewed British Journal of Sociology of Education.

The findings, based on a survey of nearly 300 principals of primary schools in England, provide new evidence of a high-stakes culture around testing where some pupils are prioritised above others and physically segregated from them.

More than a third (35%) of headteachers said SATs were the reason for grouping children into different ability sets for English, and just under half (47%) for maths, according to the results which also include in-depth interviews with school principals.

Other practices adopted by schools include targeting resources at pupils on the borderline of passing SATs at the expense of 'hopeless' cases. The most significant finding was the growth of 'intervention' sessions where children are removed from normal lessons or playtime to plug gaps in their learning and be 'fixed' academically.

The authors warn that these approaches are part of a 'potentially damaging' system where some children are made to feel inferior and which raises questions about how groupings 'might exacerbate inequalities'.

A debate is needed, they say, about the consequences for primary school children of high-pressured learning assessments, and also for staffing and resources.

"These forms of disciplinary power are encouraged by the disciplinary function of SATs themselves," says Dr Alice Bradbury from UCL Institute of Education.

"They place pressure on headteachers to prioritise results over the broader purposes of education.

"The SATs are in themselves a practice of division, designating children as at age related expectation (ARE) or not. This binary between success and failure, passing or failing, is a brutal division of children at age 11.

"Early evidence from teachers suggests that there is a strong desire for change following the (Covid) crisis, including the removal of testing."

Standard Assessment Tests (SATs) are used to assess a child's educational progress and form the basis of school league tables. The most significant (Key Stage 2) take place in May of the final year of primary education (year 6). For this type of testing, the focus of recent research has been largely international, not on how schools in England are affected or on headteachers' views.

This study involved an online survey from March to June 2019 of 288 heads about the impact of SATs in general and on issues such as staffing and extracurricular sessions. Comprehensive interviews were also conducted with 20 headteachers at a range of schools across England.

Education leaders at faith schools, academies and community primary schools were among those who took part, with 'good' the most common Ofsted rating.

The research focused on the impact on teachers and children from assessment policies which put pressure on schools.

The findings showed evidence of three approaches towards separating children in relation to SATs. The first was dividing by ability into sets, despite what the authors say is 'increasing evidence of the disadvantages'. In some schools, pupils physically moved from their normal class to different rooms/teachers, and some were even streamed permanently.

Several heads expressed concern about putting children in sets and some rejected the practice. One headteacher commented that 'pupils get into a psyche of failure because they've always been in the bottom set'.

Another approach which was commonplace involved 'booster' sessions - singling out children on the cusp of achieving a benchmark SAT grade. These are a feature of educational 'triage' where students are sorted into who will fail, pass with help, or succeed without extra support.

The authors also identified a new variant of this triage system which they say has been triggered by the 'increasing complexity of school league tables'. These involved pupils on the borderline of reaching 'greater depth' (above the expected level for year 6) who are given special support, for example, before school and during holidays.

The final practice was what the authors call 'intervention culture' where some pupils are withdrawn from normal lessons to resolve 'gaps' in their learning. They say this intensifies division by excluding those children in need of additional help from other parts of the curriculum.

The authors acknowledge that divisions created by these practices would not disappear entirely without SATs, which are currently suspended because of the pandemic. However, they suggest these tests might be replaced with 'more nuanced ways of understanding a child's attainment'. They add: "There can be no triage or 'cusp' if there is no benchmark to judge them by."

Tokyo, Japan - Scientists from Tokyo Metropolitan University have developed a new method for making ordered arrays of nanoholes in metallic oxide thin films using a range of transition metals. The team used a template to pre-pattern metallic surfaces with an ordered array of dimples before applying electrochemistry to selectively grow an oxide layer with holes. The process makes a wider selection of ordered transition metal nanohole arrays available for new catalysis, filtration, and sensing applications.

A key challenge of nanotechnology is getting control over the structure of materials at the nanoscale. In the search for materials that are porous at this length scale, the field of electrochemistry offers a particularly elegant strategy: anodization using metallic electrodes, particularly aluminum and titanium, can be used to form ordered arrays of "nanoholes" in a metallic oxide layer. By getting the conditions right, these holes adopt highly ordered patterns, with tight control over their spacing and size. These ordered porous metallic oxide films are ideal for a wide range of industrial applications, such as filtration and efficient catalysis. But to get them out of the lab and into widespread use, production methods need to become more scalable and compatible with a wider range of materials.

Enter a team led by Prof. Takashi Yanagishita of Tokyo Metropolitan University who have been pushing the boundaries of ordered nanohole array fabrication. In previous work, they developed a scalable method to make ordered nanohole arrays in aluminum oxide thin films. The team's films could be made up to 70 mm in diameter, and easily detached from the substrates they are made on. Now, they have used these films to create similar patterns using a far wider range of transition metal oxides. By using the ordered nanoporous alumina as a mask, they used argon ion milling to etch ordered arrays of shallow dimples in the surfaces of various transition metals, including tungsten, iron, cobalt and niobium. Then by anodizing the dimpled surfaces, they found that thin metallic oxide layers formed with holes where the dimples were. Previous efforts had indeed made nanoscale holes in e.g. tungsten oxide films, but the holes were not ordered, with little control over their size or spacing, making this the first time ordered nanohole arrays have been made using these transition metal oxides. On top of that, by changing the properties of the mask, they directly demonstrated how they could easily tune the spacing between the holes, making their method applicable to a wide range of nanoporous patterns with different applications.

Exciting applications are waiting for these nanostructured films, including photocatalysis, sensing applications and solar cells. The team are confident that their new scalable, tunable method for making ordered nanohole arrays with freer choice of materials will help boost efforts to bring this exciting field of nanotechnology out of the lab, and into the wider world.

Cancer cells can dodge chemotherapy by entering a state that bears similarity to certain kinds of senescence, a type of "active hibernation" that enables them to weather the stress induced by aggressive treatments aimed at destroying them, according to a new study by scientists at Weill Cornell Medicine. These findings have implications for developing new drug combinations that could block senescence and make chemotherapy more effective.

In a study published Jan. 26 in Cancer Discovery, a journal of the American Association for Cancer Research, the investigators reported that this biologic process could help explain why cancers so often recur after treatment. The research was done in both organoids and mouse models made from patients' samples of acute myeloid leukemia (AML) tumors. The findings were also verified by looking at samples from AML patients that were collected throughout the course of treatment and relapse.

"Acute myeloid leukemia can be put into remission with chemotherapy, but it almost always comes back, and when it does it's incurable," said senior author Dr. Ari M. Melnick, the Gebroe Family Professor of Hematology and Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. "A longstanding question in the field has been, 'Why can't you get rid of all the cancer cells?' A similar question can be posed for many other types of aggressive cancer in addition to AML."

For years, cancer researchers have studied how tumors are able to rebound after they appear to be completely wiped out by chemotherapy. One theory has been that because not all cells within a tumor are the same at the genetic level--a condition called tumor heterogeneity--a small subset of cells are able to resist treatment and begin growing again. Another theory involves the idea of tumor stem cells--that some of the cells within a tumor have special properties that allow them to re-form a tumor after chemotherapy has been given.

The idea that senescence is involved does not replace these other theories. In fact, it could provide new insight into explaining these other processes, Dr. Melnick said.

In the study, the researchers found that when AML cells were exposed to chemotherapy, a subset of the cells went into a state of hibernation, or senescence, while at the same time assuming a condition that looked very much like inflammation. They looked similar to cells that have undergone an injury and need to promote wound healing--shutting down the majority of their functions while recruiting immune cells to nurse them back to health.

"These characteristics are also commonly seen in developing embryos that temporarily shut down their growth due to lack of nutrition, a state called embryonic diapause," Dr. Melnick explained. "It's not a special process, but normal biological activity that's playing out in the context of tumors."

Further research revealed that this inflammatory senescent state was induced by a protein called ATR, suggesting that blocking ATR could be a way to prevent cancer cells from adopting this condition. The investigators tested this hypothesis in the lab and confirmed that giving leukemia cells an ATR inhibitor before chemotherapy prevented them from entering senescence, thereby allowing chemotherapy to kill all of the cells.

Importantly, studies published at the same time from two other groups reported that the role of senescence is important not just for AML, but for recurrent cases of breast cancer, prostate cancer and gastrointestinal cancers as well. Dr. Melnick was a contributor to one of those other studies.

Dr. Melnick and his colleagues are now working with companies that make ATR inhibitors to find a way to translate these findings to the clinic. However, much more research is needed, because many questions remain about when and how ATR inhibitors would need to be given.

"Timing will be very critical," he said. "We still have a lot to work out in the laboratory before we can study this in patients."

An interdisciplinary research team at Lehigh University has unraveled how functional biomaterials rely upon an interfacial protein layer to transmit signals to living cells concerning their adhesion, proliferation and overall development.

According to an article published today in Scientific Reports, the nanoscale features and properties of an underlying substrate do not impact the biological response of cells directly. However, these properties indirectly influence cell behavior through their control over adsorbed proteins.

In the article, "Nanostructure of bioactive glass affects bone cell attachment via protein restructuring upon adsorption," the Lehigh team demonstrates that living cells respond to interfacial layer characteristics that arise as a consequence of micro- and nano-scale structures engineered into a substrate material. These infinitesimally-tiny structures have an enormous impact upon the nature of the proteins and how they restructure themselves and electrostatically interact with the material, which in turn influences the manner in which cells attach to the substrate and develop over time.

"There are others who have studied the interfacial protein layer," says Himanshu Jain, the T.L. Diamond Distinguished Chair in Engineering and Applied Science and Professor of Materials Science and Engineering at Lehigh, who also serves as director of Lehigh's Institute for Functional Materials and Devices (I-FMD). "But this work showed directly and unambiguously for the first time how some specific nanoscale features of the substrate can impact the secondary molecular structure of the proteinated interface that in turn affects the response of the cells that are thousands of times larger."

Joining Professor Jain in guiding this research is Matthias Falk, a Professor of Cell Biology with Lehigh's College of Arts and Sciences. The team is rounded out by two doctoral students jointly supervised by Falk and Jain—Dr. Tia Kowal, who received PhD in Biological Sciences and is now a postdoctoral researcher at Stanford Medicine, and lead author Dr. Ukrit Thamma, who completed his doctorate in Materials Science and Engineering and is now a lecturer at King Mongkut's University of Technology in Bangkok, Thailand.

"Lehigh is increasingly recognized as a place where interdisciplinary team science is taking root and flourishing," says Jain. "The creation and mission of Lehigh's Interdisciplinary Research Institutes is a strategic expression of this notion—and this project is an expression of that notion in action. And the crucial role that our students play, with support from a broad faculty team, speaks for itself."

The research was published on the journal Nature Catalysis on December 14, 2020.

A strong bias towards linear and disc-shaped molecules has long been observed in drug molecules. In contrast, spherical molecules have been utilized on far fewer occasions, due to the lack of efficient access to the latter chemical space. Specifically, efficient strategies to synthesize tetraarylmethanes, a unique family of spherical molecules, have remained scarce.

Chiral tetraarylmethanes (CTAMs), a unique family of spherical molecules which bear four different aryl groups with defined stereochemistry, remain as a mystery due to the lack of efficient asymmetric synthesis. The challenge in asymmetric synthesis of CTAMs lies in not only the high barrier in making the extremely congested C?C bond connecting the central carbon and the aryl rings by conventional strategies, but also the difficulty in stereodifferentiation between the existing and likely similar aryl rings when attaching a new aryl ring to the central carbon.

"The difficulty associated with the synthesis of chiral tetraarylmethanes is that forming extremely crowded bonds around a small carbon atom requires overcoming a substantial energy barrier," said Jianwei Sun, the group's leading researcher and Professor at the Department of Chemistry, HKUST. "The other difficulty is that the bond has to be made in a defined 3D orientation. These two requirements substantially reduce the chance of success, but we were able to overcome by using a tagging strategy."

Starting from suitably tagged triarylmethanols, the protocol takes advantage of the hydrogen bonding interactions in the key para-quinone methide and indole iminium intermediates to build two libraries of enantioenriched CTAMs.

"Initially, we hypothesized that a racemic triarylmethane with a leaving group on the central carbon would be easily activated by a catalyst to generate the triarylmethyl cation intermediate," Sun continued. "We tagged two of the three aryl groups differently. When a hydroxy group is attached to one of the aryl groups, the chiral ion pair intermediate could be further stabilized as a hydrogen-bonded quinone methide (QM). The other tag then provides a secondary hydrogen bond interaction to provide the key differentiation."

Chiral spherical molecules synthesized with this method have shown promising activity against cancer cells as well as enterovirus. The group expects to establish a large and diversified library of such spherical molecules for lead optimization and structure activity relationship study, which would eventually lead to further collaborative opportunities with expertise in medicinal chemistry, chemical biology, viral biology, and pharmacology.

"High efficiency and selectivity are where our catalytic asymmetric approach really shines," noted Sun. "We are excited to start this exploration of a new paradigm of chemical space previously left overlooked."

Giving at scale by the super-wealthy has done little to redistribute wealth from rich to poor, helping perpetuate social inequalities rather than remedying them, while paying considerable dividends to donors in the form of privilege and influence in society and politics, new research shows.

In the research paper 'Elite philanthropy in the United States and the United Kingdom in the new age of inequalities' researchers at the University of Bath School of Management and Newcastle University Business School also conclude that giving by the super-wealthy has failed significantly to benefit poor countries in the developing world, contrary to popular belief.

"This is a difficult area for many to come to terms with - it can be argued that any philanthropy is a good thing and that holds true if it is genuinely altruistic. But what we have identified is that elite philanthropy may actually be perpetuating inequality by favouring elite causes, by increasing the influence and power of the super-rich, and by increasing tolerance of inequalities by ordinary people," said Professor Mairi Maclean of the University of Bath School of Management.

Maclean said the research shows how elite philanthropy conspicuously increases the social standing of the super-wealthy, with donors receiving honours, distinctions and favourable media coverage. She said much elite philanthropy supports elite causes and institutions, a source of prestige for donors but a factor in sustaining or even increasing social inequality.

Maclean acknowledged that some very wealthy people have given away sizeable parts of their fortunes but said the research shows that most of their peers do not, with combined donations amounting to only a small percentage of the total wealth of the super-rich. "The fact is most super-wealthy people give very little relative to their means."

Her co-researcher at Newcastle University Business School, Professor Charles Harvey, said, "The greater part of funding stays at home in developed countries. The Bill and Melinda Gates Foundation is one of a handful of foundations to embrace international development, but even in this case much of the spend is on research and development in developed countries. Development funding by philanthropic foundations is in fact dwarfed by taxpayer funded spending on overseas development assistance."

The research shows that funding frequently comes with strings attached, with the super-rich able to pursue personal and political agendas through major charitable foundations. Some, by dint of their financial clout, are able to influence governments and the prestigious educational institutions that attract a major part of high-end donations.

"Universities like Harvard and Yale in the United States, and Oxford and Cambridge in the UK gobble up the lion's share of philanthropic funding, conferring on them a significant competitive advantage and arguably sustaining social inequality," Maclean added.

Maclean said the research team identified several incentives for elite philanthropists, including the amassing of 'social and cultural capital', such as receiving honours like as knighthoods in the United Kingdom for their services to charity. Viewed in this light, donors can effectively buy their way into circles of influence and networks. Tax advantages also play a part.

"In both the US and UK, philanthropists have their giving power boosted by being able to offset their donations against their tax bills. This looks, on the face of it, like a good thing to encourage giving. But it means those funds can be diverted into areas in which they have an interest or wish to exert influence or gain prestige. They, rather than governments, are effectively deciding how and where their taxes should be spent," Harvey said.

Maclean said attempts to reform this tax issue - most notably an initiative by former British Chancellor George Osborne to put a cap on tax relief on donations - had failed in the recent past. Philanthropists had almost universally opposed any changes to a system that many critics believe is an unjustifiable form of state conferred elite privilege.

"It is easy to be cynical about this. We do accept that many elite philanthropists act sincerely to improve the lives of others and that there are many generous and outstanding philanthropists, but we suggest that altruism alone does not explain their actions. It is far more likely that philanthropy yields substantive rewards beyond the emotional satisfactions of beneficence - and our research bears this out," Maclean said.

DALLAS, March 11, 2021 — Discriminatory housing policies that restricted the sale or purchase of homes by race in certain neighborhoods across the U.S., called ‘redlining,’ which were established nearly a century ago and outlawed by the Fair Housing Act of 1968, were associated with higher rates of stroke in the same neighborhoods in 2017, according to preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2021. The virtual meeting is March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

“Differences in stroke rates, whether we are studying ischemic or hemorrhagic stroke, are usually attributed to biological differences or differences in underlying conditions,” said lead study author Jeffrey J. Wing, Ph.D., M.P.H., an assistant professor of epidemiology in the College of Public Health at The Ohio State University in Columbus, Ohio. “Yet, our findings suggest the difference we found in the Columbus area may actually be the result of structural racism.”

Beginning in 1936, the Home Owners’ Loan Corporation began restricting the sale of homes in certain neighborhoods across the country by redlining or marking neighborhoods by “risk for investment,” which equated to race. As a result, residents who lived within these redlined areas were denied home loans, which lowered tax revenues in these communities, thereby reducing investment in schools and services, and creating numerous inequities for residents for multiple generations.

“Even though redlining was abolished in 1968, redlining is a form of structural racism that perpetuated segregation and racial inequities. Accumulating evidence shows this divisive and exclusionary housing practice continues to have long-term effects on the health of many people, even today – more than 80 years later,” said study co-author Helen Meier, Ph.D., M.P.H., assistant research scientist at University of Michigan’s Institute for Social Research. ”Our study is one of the first to link historic redlining in a U.S. city to frequency of stroke.”

Researchers examined the association between the discriminatory housing policies of redlining and stroke rates in Columbus, Ohio neighborhoods in 2017. They calculated historic redlining scores for neighborhoods within the boundaries of Columbus based on the degree of redlining. Thus, the greater the redlining, the higher the redlining score.

Researchers then matched the redlining scores with stroke rates measured in the same neighborhoods from the 500 Cities Project. The 500 Cities Project is from the U.S. Centers for Disease Control and Prevention and reports on 27 chronic disease measures for the 500 largest American cities in all 50 states, quantified by city and census tract-level data. They assessed the association between historic redlining scores and stroke rates across neighborhoods in Columbus in 2017.

Researchers found:

Higher historic redlining scores were associated with greater rates of stroke, when comparing the highest to the lowest quartile of historic redlining scores. 
Neighborhoods in the highest group of historic redlining scores had a 1.48% higher stroke rate, compared to those with the lowest redlining scores.

“As different cities across the country declare racism as a public health crisis, it’s important to have more research that shows the link between racism and health disparities,” Wing said. “Our research has the potential to help change how we treat and care for all individuals and promote equitable access to care that can lead to improved health outcomes.”

“Health disparities in stroke are going to persist until we address the legacy of structural racism, of which historical redlining is one form,” Meier said. “It’s important to document the significant, negative impacts of structural racism on health.”

Study limitations include people who had a history of stroke may not have always resided in the same census tract, leading to unmeasured variability in redlining exposure. In addition, this is an ecologic-designed study, where redlining exposure was combined with stroke rate to a neighborhood level, which limits the assessment of individual associations, Wing added.

The American Heart Association recently published a presidential advisory that names structural racism as a cause of poor health and premature death from heart disease and stroke. The advisory, titled “Call to Action: Structural Racism as a Fundamental Driver of Health Disparities,” reviews the historical context, current state and potential solutions to address structural racism in the U.S. and outlines steps the Association is taking to address and mitigate the root causes of health care disparities.

To highlight tumours in the body for cancer diagnosis, doctors can use tiny optical probes (nanoprobes) that light up when they attach to tumours. These nanoprobes allow doctors to detect the location, shape and size of cancers in the body.

Most nanoprobes are fluorescent; they absorb light of a specific colour, like blue and then emit back light of a different colour, like green. However, as tissues of the human body can emit light as well, distinguishing the nanoprobe light from the background light can be tough and could lead to the wrong interpretation.

Now, researchers at Imperial College London have developed new nanoprobes, named bioharmonophores and patented at Imperial, which emit light with a new type of glowing technology known as second harmonic generation (SHG).

After testing the nanoprobes in zebrafish embryos, the researchers found that bioharmonophores, which were modified to target cancer cells, highlighted tumours more brightly and for longer periods than fluorescent nanoprobes. Their light can be easily spotted and distinguished by the tissue generally emitted light, and they also attach precisely to tumour cells and no healthy cells, making them more precise in detecting tumour edges.

Lead researcher Dr Periklis Pantazis of Imperial's Department of Bioengineering said: "Bioharmonophores could be a more effective way to detect tumours than is currently available. They uniquely combine features that could be great for cancer diagnosis and therapy in clinical practice and could eventually improve patient outcomes following further research."

The findings are published in ACS Nano.

Bioharmonophores are both biocompatible and biodegradable as they are made of peptides - the same ingredients of proteins found in the body. They are metabolised naturally in the body within 48 hours and are therefore unlikely to pose long-term health risks.

To investigate precise tumour detection, the researchers first injected zebrafish embryos with malignant cancer cells, which allowed tumour cells to proliferate unchecked. Twenty-four hours later they injected bioharmonophores which were modified to target p32 peptide molecules that are specifically found in tumour cells. They then used imaging techniques at Imperial's Facility for Imaging by Light Microscopy to study how well the modified bioharmonophores detected the tumours.

They found that bioharmonophores had outstanding detection sensitivity, meaning they attached to specific tumour cells but not to healthy ones. Fluorescence-enabled nanoprobes tend to attach less specifically, meaning they can misrepresent healthy cells as tumour cells, or vice versa.

They also found that unlike fluorescence, bioharmonophores did not 'bleach', meaning they did not lose their ability to emit light over time. In addition, the light emitted by bioharmonophores did not saturate as happens with fluorescent nanoprobes, meaning they got brighter when illuminated with more light. This way tumours became even clearer.

Dr Pantazis said: "It is very important that tumour nanoprobes highlight cells specifically and clearly for cancer diagnosis. Our proof-of-concept study suggests that the very bright bioharmonophores could be powerful tools in diagnosing cancer and targeting treatments in the coming years."

The manufacture of bioharmonophores is cheap, reproducible, scalable and takes around two days at room temperature. They now need to be tested in mammals to identify how well the findings translate beyond zebrafish.

The researchers are also looking into how bioharmonophores could be used to guide surgical interventions during cancer surgery, as well as how they could generate light at different frequencies to potentially help kill tumour cells with high precision.